TREM-2 serves as a negative immune regulator through Syk pathway in an IL-10 dependent manner in lung cancer
Metrics: PDF 2622 views | HTML 3123 views | ?
Yinan Yao1,*, Hequan Li1,*, Junjun Chen1, Weiyi Xu2, Guangdie Yang1, Zhang Bao1, Dajing Xia3,4, Guohua Lu1, Shuwen Hu1, Jianying Zhou1
1Department of Respiratory Diseases, First Affiliated Hospital of Zhejiang University, Hangzhou, China
2Department of Clinical Laboratory, First Affiliated Hospital of Zhejiang University, Hangzhou, China
3School of Public Health, Zhejiang University, Institute of Immunology, Zhejiang University, Hangzhou, China
4Institute of Immunology, Zhejiang University, Hangzhou, China
*These authors have contributed equally to this work
Jianying Zhou, email: [email protected]
Hequan Li, email: [email protected]
Keywords: TREM-2, lung cancer, IL-10, Syk, immunoregulation
Received: October 20, 2015 Accepted: March 28, 2016 Published: April 18, 2016
During infection, triggering receptor expressed on myeloid cells-2 (TREM-2) restrains dendritic cells (DCs) and macrophages (MΦs) phagocytosis, as well as reduces pro-inflammatory cytokines release through DNAX-activation protein 12 (DAP12) signaling. However, the role of TREM-2 signaling in cancer has never been elucidated. In the current study, we found that TREM-2 was up-regulated on peripheral blood monocytes in tumor-bearing host. More TREM-2+DCs were detected in the lung of 3LL tumor-bearing mice. On the other hand, the level of TREM-2 on pulmonary MΦs positively correlated with the pathological staging of lung cancer. However, surgical or chemotherapeutic reduction of tumor burden led to the obvious decline of TREM-2. In vitro, TREM-2 expression of bone marrow (BM)-derived DCs and MΦs was induced by conditional medium (CM) containing the supernatant of 3LL cells. TREM-2+DCs from CM and/or tumor-bearing mice held altered phenotypes (CD80LowCD86LowMHCIILow) and impaired functions, such as, reduced interleukin (IL)-12 secretion, increased IL-10 production, and weakened ovalbumin (OVA)-endocytic capacity; also developed potent inhibitory effect on T cell proliferation that could be partially reversed by TREM-2 blockage. Moreover, spleen tyrosine kinase (Syk) inhibitor restrained IL-10 production of TREM-2+DC. Remarkably, IL-10 neutralizing antibody and Syk inhibitor both lowered the suppressive potential of TREM-2+DCs in T cell proliferation. Also, adoptive transfer of this TREM-2+DCs accelerated the tumor growth rather than jeopardized survival in lung cancer-bearing mice. In conclusion, these results indicate that TREM-2 might act as a negative immuno-regulatory molecule through Syk pathway in an IL-10 dependent manner and partially predicts prognosis in lung cancer patients.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.